We administered dCF and IFN-alpha sequentially to pts. with HCL in an attempt to improve the response rate and duration observed in earlier studies using each drug alone. In this study, we evaluated pts. for response by performing bilateral iliac crest bone marrow biopsies and aspirates since the peripheral blood normalizes rapidly after either IFN-alpha or dCF treatment but disease becomes patchy in the bone marrow and might be missed if only unilateral bone marrow biopsies had been performed. Other studies using IFN-alpha or dCF alone used unilateral marrow examinations in evaluating response. Using these more relaxed criteria of response, authors had published high rates of complete remission to dCF. Of 15 pts. entered in our study, 14 are evaluable for response with 1 pt. having diffuse osteosclerosis not being evaluable for marrow response. All pts. had rapid normalization of peripheral blood counts and all 14 marrow-evaluable pts. were found to have very small numbers (less than 5% of total marrow cellularity) of residual hairy cells at the completion of tx. Among the 14 evaluable pts., 4 pts. have developed progressive disease off tx. The single nonevaluable pt. with diffuse osteosclerosis developed anemia with increasing sIL-2R levels consistent with progressive hairy cell leuk- emia. 3 pts. received tx. With 2-chlorodeoxyadenosine and 1 received IFN-alpha. Although the initial response rate to the combination of dCF and IFN appears to be no better than that observed with dCF alone, the response duration may be longer. The remaining pts. continue to be followed for determination of response duration.